Pella was inhabited as early as 5000 BC, and Egyptian texts make reference to it in the 2nd millennium BC.
Pella really only flourished during the Greek and Roman periods. The Jews largely destroyed Pella in 83 BC because the inhabitants were not inclined to adopt the customs of their conquerors. It was to Pella that Christians fled persecution from the Roman army in Jerusalem in the 2nd century AD.
The city reached its peak during the Byzantine era, and by AD 451 Pella had its own bishop. The population at this time may have been as high as 25, 000. The defeat of the Byzantines by the invading Islamic armies near Pella in 635 was quickly followed by the knockout blow at the Battle of Yarmouk (near modern Mukheiba) the next year.
Until the massive earthquake that shook the whole region in 747, Pella continued to prosper under the Umayyads. Archaeological finds show that even after the earthquake the city remained inhabited on a modest scale. The Mamluks occupied it in the 13th and 14th centuries, but afterwards Pella was virtually abandoned.